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In vivo anti-tumor effects of 3-BP, sorafenib, and a combination treatment in xenograft nude mice bearing AR Huh-BAT cells.

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posted on 31.03.2017, 18:04 by Minjong Lee, Ara Jo, Seulki Lee, Jong Bin Kim, Young Chang, Joon Yeul Nam, Hyeki Cho, Young Youn Cho, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim

(A) Tumor growth rates in the combination treatment group were significantly lower than those in the control, sorafenib, or 3-BP treatment group (upper panel). Gross images of tumors before treatment, tumors from the control group, and tumors from the combination treatment group are shown (lower panel). (B) In vivo demonstration of the apoptosis-inducing efficacy in the control, 3-BP, sorafenib, and combination treatment group was shown: H & E and TUNEL staining of tumor tissues in the control, sorafenib, 3-BP, and combination-treated mice (×40 magnification). (C) TUNEL-positive cell percentages (apoptotic index) were determined in six different high power (×400 magnification) fields. (D) There was a significant difference in body weight between the control group and the combination treatment group (P<0.05). (E) After matrix detachment, anoikis-resistant cancer cells decrease intracellular ROS levels through inducing enzymes involved in the glycolysis and antioxidant systems for their survival. The Warburg effect can be modulated by increased intracellular ROS levels. Increased ROS levels induce HK II expression and make cancer cells sensitive to 3-BP treatment, and thereby promote cell death via ROS-mediated apoptosis (the black box indicates monocarboxylate transporter-1, and the white box indicates monocarboxylate transporter-4). *P<0.05; **P<0.01; ***P<0.001. Abbreviation: AR, anoikis-resistant; BSO, buthionine sulfoximine; 3-BP, 3-bromopyruvate.